The objectives of this project are to address the following questions and hypotheses related to hematopoietic transplantation for treatment of AML. During the previous grant period we developed a promising strategy. Using less-toxic, non-ablative preparative regimens for allogeneic transplantation, allowing engraftment and development of graft-vs.-leukemia responses and examined strategies to separate GVL from GVHD. We also established fludarabine as an effective immunosuppressive agent for hematopoietic transplantation and developed an intravenous form of bufsulfan for BMT applications. We also generated dendritic cells from leukemic precursors which stimulate autologous or allogeneic reactivity against AML. We extend these studies and will answer the following questions and hypotheses: 1) Can purine analog based non-ablative preparative regimens with allogeneic HSCT induce durable remissions in high-risk patients with AML as initial therapy or consolidation of initial remission? 2) What is optimal dose and schedule of busulfan and fludarabine in allogeneic HSCT in patients with recurrent AML? 3) Can leukemic dendritic cell primed autologous or allogeneic T-cells induce anti-leukemic responses in vivo? 4) Does resistance to apoptosis affect the response of AMP to adoptive immunotherapy.? This will be examined by studying induction of apoptosis in vitro in patients responding or not responding to these immunotherapeutic approaches. The ultimate goal of this project is to more efficiently induce graft-vs-leukemia as a primary therapy for AML.